Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats

We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR-α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations. Cinnamon polyphenol decreased body weight, visceral fat, liver weight and serum glucose and insulin concentrations, liver antioxidant enzymes, and lipid profile (P<0.05) and reduced serum and liver MDA concentration compared to HFD rats (P<0.05). Cinnamon polyphenol also suppressed the hepatic SREBP-1c, LXR-α, ACLY, FAS, and NF-κB p65 expressions and enhanced the PPAR-α, IRS-1, Nrf2, and HO-1 expressions in the HFD rat livers (P<0.05). In conclusion, cinnamon polyphenol reduces the hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathway in HFD rat liver

Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-κB pathway in high-fat diet fed and Streptozotocin-induced diabetic rats

<p>Abstract</p> <p>Background</p> <p>Diabetic nephropathy is one of major complications of diabetes mellitus. Although chromium is an essential element for carbohydrate and lipid metabolism, its effects on diabetic nephropathy are not well understood. The present study was conducted to investigate the effects of chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB) and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney.</p> <p>Methods</p> <p>Male Wistar rats were divided into six groups. Group I received a standard diet (8% fat) and served as a control; Group II was fed with a standard diet and received CrPic; Group III was fed with a standard diet and received CrHis; Group IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ) but supplemented with CrPic for 12 weeks. Group VI was treated as group IV (HFD/STZ) but supplemented with CrHis.</p> <p>Results</p> <p>The increased NF-κβ p65 in the HFD/STZ group was inhibited by CrPic and CrHis supplementation (<it>P </it>< 0.05). In STZ-treated rats, a significant decrease in levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) was found in kidney tissues when compared to control rats (<it>P </it>< 0.05). A significant increase in the levels of IκBα was observed in CrPic- and CrHis-treated rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly decreased in diabetic rats compared with the control rats. There was a higher tendency for increase of kidney Nrf2 level and decrease in kidney NFκBp65 levels and 4- hydroxyl nonenal (4-HNE) protein adducts (<it>P </it>< 0.05) in diabetic rats.</p> <p>Conclusion</p> <p>Our result show that in kidney tissue CrHis/CrPic increases Nrf2 level, parallelly decreases NF-κB and partially restores IκBα levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in antioxidant defense system via the Nrf2 pathway by reducing inflammation through NF-κβ p65 inhibition. Moreover, a greater reduction in NF-κB expression and greater increases in expressions of IκBα and Nrf2 in diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest that CrHis has more favorable effects than CrPic.</p

Effects of the changes between preand post-treatment 18F-FDG PET-CT volumetric parameters on overall survival in pleural mesothelioma

Introduction. This study aimed to examine the efficacy of positron emission tomography in fusion with computed tomography (PET-CT) parameters in predicting survival outcomes for patients with malignant pleural mesothelioma.  Material and methods. This study retrospectively evaluated the data of 250 patients who were followed up after a diagnosis of malignant pleural mesothelioma. The relationship of pre-treatment [maximum standardized uptake value (SUVmax1), metabolic tumor volume (MTV1), total lesion glycolysis (TLG1), tumor/background (TBR1), pleural thickness1), post-treatment (SUVmax2, MTV2, TLG2, TBR2, pleural thickness2], and DPET-CT parameters with survival was retrospectively evaluated in 36 patients whose pre- and post-treatment CT scan examinations were complete.  Results. The median age of the patients was 57.5 years, ranging from 35 to 76. Median follow-up time was 16 months, with a range of 7 to 42 months. Median survival was calculated as 18.8 months for all patients. Based on the determined cut-off values, overall survival was determined as 29.9 months in patients with TLG2 ≤ 158 compared to 16 months in patients with TLG2 &gt; 158 (p = 0.009) and as 30.9 months in patients with DTLG ≤ –62.58 compared to 16 months in patients with DTLG &gt; –62.58 (p = 0.001). In addition, median overall survival (OS) was determined as 29.9 months in patients with MTV2 ≤ 63.9 compared to 16 months in patients with MTV2 &gt; 63.9 (p = 0.007) and as 29.9 months in patients with DMTV ≤ –54.03 compared to 16 months in patients with DMTV &gt; –54.03 (p = 0.002). When evaluated with respect to TBR2; median OS was 29.9 months in patients with TBR2 ≤ 1.84 compared to 16 months in patients with TBR2 &gt; 1.84 (p = 0.039).  Conclusions. Our research findings indicate a correlation between OS and volumetric PET-CT measures, specifically TLG and MTV

Preeklamptik gebelerde ve preeklampsi öyküsü olan kadinlarda dolaşımdaki endotel hücrelerinin endotel disfonksiyonu ile ilişkisi

Preeklamptik Gebelerde ve Preeklampsi Öyküsü olan Kadınlarda Dolaşımdaki Endotel Hücrelerinin Endotel Fonksiyonu ile İlişkisi AMAÇ: Bu çalışmada preeklampsisi olan ve daha önceden preeklampsi geçirmiş kadınlarda dolaşımdaki endotel hücresi ile diğer endotel disfonksiyonu parametreleri ve VEGF reseptör 1 düzeylerinin arasındaki ilişkiyi göstermeyi hedefledik. GEREÇ ve YÖNTEM: Marmara Üniversitesi Hastanesi Kadın ve Doğum Hastalıkları kliniğine Kasım 2009 – Aralık 2011 tarihleri arasında başvuran 17 preeklampsi hastası, 21 sağlıklı gebe, preeklampsi hikayesi olan 16 kadın ve sağlıklı gebelik geçirmiş 24 kadın çalışmaya dahil edildi. Dolaşımdaki endotel hücresi (DEH), akıma bağlı dilatasyon (FMD), adezyon molekülleri ve vasküler endotelyal büyüme faktörü reseptör-1 (VEGFR-1) ölçümleri yapıldı. Spot idrarda mikroalbumin/kreatinin oranı tespit edildi. BULGULAR: Preeklamptik gebelerde DEH sayısı (9.9 ± 7.9 vs 3.0 ± 4.1 hücre/ml, p<0.0005), solubl vasküler adezyon molekülü (sVCAM-1) ve sE-selectin düzeyleri (825 vs 404 ng/ml ve 69 vs 37 ng/ml, p<0,0005) ve sVEGFR-1 optik dansite değerleri (1.087 vs 0.40, p<0.001) sağlıklı gebelere göre daha yüksek saptanırken solubl interselüler adezyon molekülü (sICAM-1) düzeyleri benzerdi. Preeklampsi hikayesi olan kadınlarda DEH sayıları, FMD değerleri, idrarda albumin/kreatinin oranları, sVCAM-1, sICAM-1, sE-selectin düzeyleri sağlıklı gebelik geçirmiş kadınlarla benzerdi. Preeklampsi geçirmiş kadınlarda sVEGFR-1 optik dansite ölçümleri ise daha yüksekti (0.165 vs 0.136 p<0.05). SONUÇ: Preeklampsi hastalarında endotel hasarı, aktivasyonu ve disfonksiyonunun artmış olduğu ve sVEGFR-1 düzeylerinin yükseldiği saptanmıştır. Preeklampsi hikayesi olan kadınlarda devam eden endotel hasar ve disfonksiyon bulgusu saptanmayıp, bu kişilerde yüksek saptanan sVEGFR-1 düzeylerinin klinik anlamının ortaya konması için daha fazla çalışmaya ihtiyaç bulunmaktadır. Anahtar kelimeler, preeklampsi, mikroalbuminüri, dolaşımdaki endotel hücresi, akıma bağlı dilatasyon, vasküler büyüme faktörü reseptörü-1, adezyon molekülleri Circulating Endothelial Cells and Endothelial Dysfunction in Preeclamptic Pregnancies and in Women with History of Preeclampsia AİM: The aim of this study was to evaluate circulating endothelial cells ( CEC ) and the relationship between CEC and endothelial dysfunction and vascular endothelial growth factor receptor-1 ( VEGFR-1 ) levels in preeclamptic pregnancies and in women who have a history of preeclampsia. METHOD and MATERIALS: Seventeen preeclamptic pregnant women, 21 healthy pregnant women, 16 non-pregnant women with a history of preeclampsia in the past pregnancies and 24 healthy non-pregnant women who have attended to Gynecology&Obstetrics Clinics of Marmara University Hospital between November 2009 and December 2011 are included in this study. The number of CECs, flow mediated vasodilation (FMD), levels of adhesion molecules and VEGFR-1, and urine albumin/creatinine ratio were determined in the study population. RESULTS: CEC numbers ( 9.9 ± 7.9 vs 3.0 ± 4.1 cell/ml, p<0.0005), sVCAM-1 levels (soluble vascular adhesion molecule ) and sE-selectin levels (825 vs 404 ng/ml and 69 vs 37 ng/ml, p<0,0005) were higher in preeclamptic pregnant women in relation to healthy pregnant women. sICAM-1 (intercellular adhesion molecule) levels were similar between these two groups. CEC numbers, FMD values, levels of adhesion molecules and levels of urine albunin/creatinine ratio were similar between women with previous history of preeclampsia and healthy non-pregnant women with previous history of healthy pregnancy. sVEGFR-1 optic density values were higher in women with previous history of preeclampsia (0.165 vs 0.136, p<0.05). COCLUSION: Markers of endothelial activation, dysfunction and damage were increased in preeclamptic patients. sVEGFR-1 levels are also increased in both preeclamptic women and the ones with a history of preeclampsia. We didn’t find a sign of endothelial damage, activation and dysfunction in non-pregnant women with history of preeclampsia in the past pregnancies. There is a need for more investigations to evaluate higher sVEGFR-1 levels in this group of patients. Keywords, preeclampsia, microalbuminuria, endothelial cell, flow mediated vasodilation, adhesion molecule, vascular growth factor recepto

Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway

WOS: 000314541600001PubMed ID: 23311701Background: Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side-effects such as nephrotoxicity and ototoxicity. Cisplatin chemotherapy induces a reduction in the antioxidant status, leading to a failure of the antioxidant defense against free-radical damage generated by antitumor drugs. Cisplatin-induced oxidative stress in the kidney was partially prevented by antioxidant treatments using superoxide dismutase, glutathione, selenium and flavonoids. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. However, the mechanism of the protective effects of melatonin against cisplatin-induced nephrotoxicity is still essentially unknown. We therefore designed this study to investigate the underlying mechanism of the protective effect of melatonin against cisplatin-induced renal damage in a rat nephrotoxicity model in vivo. Methods: Twenty eight 8-week-old male Wistar rats were divided into four groups of control, melatonin treatment (4 mg/kg b.w i.p. for 10 days), cisplatin treatment (7 mg/kg b.w., i.p.) and melatonin and cisplatin combination treatment. Serum urea nitrogen (urea-N) and creatinine levels were measured. Histopathological changes were evaluated. In addition, we analyzed the expression levels of HO-1, Nrf2, NF-kappa B and AP-1 in Western blot analysis. Results: Both serum creatinine and urea nitrogen increased significantly following cisplatin administration alone; these values decreased significantly with melatonin co-treatment of cisplatin-treated rats. Histological analysis showed that cisplatin caused damage in the proximal tubular cells in the kidneys of cisplatin-treated rats; these changes were reversed by melatonin co-treatment. Upon Western blot analysis, melatonin treatment increased Nrf2 accumulation in the nuclear fraction, and increased the expression of HO-1 in the cytosolic fraction as compared to the cisplatin-treated rats. Expressions of NF-kappa B p65 and AP-1 were increased significantly in the kidneys of rats treated with cisplatin compared with the expression in the kidneys from the control, melatonin-only-treated and melatonin co-treated rats. Conclusion: Our present data suggest that melatonin attenuates cisplatin-induced nephrotoxicity possibly by modulating Nrf2/HO-1 signaling.EMBO (European Molecular Biology Organization) installation grant; Turkish Academy of Sciences (TUBA)This work was supported by EMBO (European Molecular Biology Organization) installation grant and The Turkish Academy of Sciences (TUBA)

MANGO GINGER SUPPLEMENTATION MAY PROTECT BONE DAMAGE INDUCED BY METHOTREXATE IN RATS

Mango ginger (MG) has antiinflammatory and antioxidant properties. The objective of this study was to investigate the potential protective role of MG and the mechanisms against methotrexate (MTX) induced bone damage in rats. A total of 28 Sprague-Dawley rats were divided into four groups: i) control; ii) MG, rats were treated orally with 50 mg/kg/day of MG, iii) MTX, rats were injected with 0.75 mg/kg of MTX from 8th to 12th day for 5 days and iv) MTX+MG group, rats were treated with 50 mg/kg/day of MG and injected with MTX from 8th to 12th day for 5 days. MTX pretreatment increased blood urea nitrogen and creatinine levels and aminotransferase enzyme activities, while tibia osteocalcin levels and bone mineral density (BMD) decreased (p < 0.001). MG pretreatment markedly attenuated aminotransferases activities and creatinine levels and increased tibia osteocalcin levels and femur BMD in the MTX + MG groups. MTX treatment increased levels of bone nuclear factor kappa beta ligand receptor-activator (RANKL), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and decreased the bone osteoprotegerin (OPG) and type1 collagen levels (p < 0.001). The effect of MG treatment on RANKL, IL-6, TNF-α, OPG and type1 collagen levels induced by MTX was observed actual effects (p < 0.05). Similarly, the protective effect of MG against MTX was confirmed by histological examination. In conclusion, MG pretreatment reduced the negative effects of MTX on bone damage by improving BMD and modulation of RANKL, IL-6, TNF-α, OPG and type1 collagen expressions in the rats

Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway

Abstract Background Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side-effects such as nephrotoxicity and ototoxicity. Cisplatin chemotherapy induces a reduction in the antioxidant status, leading to a failure of the antioxidant defense against free-radical damage generated by antitumor drugs. Cisplatin-induced oxidative stress in the kidney was partially prevented by antioxidant treatments using superoxide dismutase, glutathione, selenium and flavonoids. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. However, the mechanism of the protective effects of melatonin against cisplatin-induced nephrotoxicity is still essentially unknown. We therefore designed this study to investigate the underlying mechanism of the protective effect of melatonin against cisplatin-induced renal damage in a rat nephrotoxicity model in vivo. Methods Twenty eight 8-week-old male Wistar rats were divided into four groups of control, melatonin treatment (4 mg/kg b.w i.p. for 10 days), cisplatin treatment (7 mg/kg b.w., i.p.) and melatonin and cisplatin combination treatment. Serum urea nitrogen (urea-N) and creatinine levels were measured. Histopathological changes were evaluated. In addition, we analyzed the expression levels of HO-1, Nrf2, NF-κB and AP-1 in Western blot analysis. Results Both serum creatinine and urea nitrogen increased significantly following cisplatin administration alone; these values decreased significantly with melatonin co-treatment of cisplatin-treated rats. Histological analysis showed that cisplatin caused damage in the proximal tubular cells in the kidneys of cisplatin-treated rats; these changes were reversed by melatonin co-treatment. Upon Western blot analysis, melatonin treatment increased Nrf2 accumulation in the nuclear fraction, and increased the expression of HO-1 in the cytosolic fraction as compared to the cisplatin-treated rats. Expressions of NF-κB p65 and AP-1 were increased significantly in the kidneys of rats treated with cisplatin compared with the expression in the kidneys from the control, melatonin-only-treated and melatonin co-treated rats. Conclusion Our present data suggest that melatonin attenuates cisplatin-induced nephrotoxicity possibly by modulating Nrf2/HO-1 signaling.</p